ArticleActa neuropathologica communications2014
Conformational specificity of the C4F6 SOD1 antibody; low frequency of reactivity in sporadic ALS cases.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Reliable repurposing of the antibody interactome inside the cell.Nature communications · 2026Article
- Diverse effects of coexpression of human SOD1 variants on motor neuron disease.Human molecular genetics · 2025Article
- A structure-guided antibody detects SOD1 oligomers in diverse ALS genotypes.bioRxiv : the preprint server for biology · 2025Article
- Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells.Structure (London, England : 1993) · 2024Article
- Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology.Nature communications · 2024Article
- Phenotypic diversity in ALS and the role of poly-conformational protein misfolding.Acta neuropathologica · 2021Review
- Variation in the vulnerability of mice expressing human superoxide dismutase 1 to prion-like seeding: a study of the influence of primary amino acid sequence.Acta neuropathologica communications · 2021Article
- A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells.International journal of molecular sciences · 2021Article
- Novel SOD1 monoclonal antibodies against the electrostatic loop preferentially detect misfolded SOD1 aggregates.Neuroscience letters · 2021Article
- Passive immunotherapies targeting Aβ and tau in Alzheimer's disease.Neurobiology of disease · 2020Review
- Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?Translational neurodegeneration · 2020Review
- Tryptophan residue 32 in human Cu-Zn superoxide dismutase modulates prion-like propagation and strain selection.PloS one · 2020Article
- Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis.Molecular neurodegeneration · 2019Article
- Misfolded SOD1 inclusions in patients with mutations inJournal of neurology, neurosurgery, and psychiatry · 2019Article
- AAV2/9-mediated overexpression of MIF inhibits SOD1 misfolding, delays disease onset, and extends survival in mouse models of ALS.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension.Acta neuropathologica · 2019Article
- Experimental Mutations in Superoxide Dismutase 1 Provide Insight into Potential Mechanisms Involved in Aberrant Aggregation in Familial Amyotrophic Lateral Sclerosis.G3 (Bethesda, Md.) · 2019Article
- Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis.Scientific reports · 2018Article
- Investigation of Anti-SOD1 Antibodies Yields New Structural Insight into SOD1 Misfolding and Surprising Behavior of the Antibodies Themselves.ACS chemical biology · 2018Article
- Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Greater than 160 missense mutations in copper-zinc superoxide dismutase-1 (SOD1) can cause amyotrophic lateral sclerosis (ALS). These mutations produce conformational changes that reveal novel antibody binding epitopes. A monoclonal antibody, clone C4F6 - raised against the ALS variant G93A of SOD1, has been identified as specifically recognizing a conformation shared by many ALS mutants of SOD1. Attempts to determine whether non-mutant SOD1 adopts a C4F6-reactive conformation in spinal tissues of sporadic ALS (sALS) patients has produced inconsistent results. To define the epitope recognized by C4F6, we tested its binding to a panel of recombinant ALS-SOD1 proteins expressed in cultured cells, producing data to suggest that the C4F6 epitope minimally contains amino acids 90-93, which are normally folded into a tight hairpin loop. Multiple van der Waals interactions between the 90-93 loop and a loop formed by amino acids 37-42, particularly a leucine at position 38, form a stable structure termed the β-plug. Based on published modeling predictions, we suggest that the binding of C4F6 to multiple ALS mutants of SOD1 occurs when the local structure within the β-plug, including the loop at 90-93, is destabilized. In using the antibody to stain tissues from transgenic mice or humans, the specificity of the antibody for ALS mutant SOD1 was influenced by antigen retrieval protocols. Using conditions that showed the best discrimination between normal and misfolded mutant SOD1 in cell and mouse models, we could find no obvious difference in C4F6 reactivity to spinal motor neurons between sALS and controls tissues.
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